Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis
Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis
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DOI：
10.1073/pnas.0403423101
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发表时间：
2004-06-29
影响因子：
11.1
通讯作者：
Vasil, ML
中科院分区：
文献类型：
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作者：
Wilderman, PJ;Sowa, NA;Vasil, ML
在许多细菌中，铁的动态平衡主要由铁摄取调节器(Fur)控制，Fur是一种转录抑制因子。然而，一些基因，包括那些与铁储存有关的基因，受到毛皮的正向调控。在大肠杆菌中发现了一种Fur抑制的调节性小RNA(SRNA)RyhB，研究表明该SRNA对基因的负调控与Fur对某些基因的正调控有关。在铜绿假单胞菌中没有发现RyhB序列同源物，尽管鉴定出受其毛皮同源物正调控的基因。生物信息学方法在铜绿假单胞菌中发现了两个串联sRNA，它们是RyhB的功能同源物的候选者。这些sRNA(PrrF1和PrrF2)彼此95%相同，并且每个sRNA前面都有一个功能毛发盒。它们的表达是在铁限制下诱导的。这两个sRNA的缺失都需要影响一系列基因的铁依赖调节，包括那些参与抗氧化性应激、铁储存和中间代谢的基因。与在大肠杆菌中一样，PrrF sRNAs的诱导导致超氧化物歧化酶(SODB)、琥珀酸脱氢酶(SDH)和编码细菌铁蛋白的基因的mRNAs迅速丢失。因此，PrrF sRNAs是RyhB sRNA的功能同源物。至少有一个基因BFRB受到Fur和Fe2+的正调控，即使在没有PrrF sRNAs的情况下也是如此。这项工作表明，sRNA在细菌铁稳态中的作用可能是广泛的，类似于这里描述的方法可能会在其他生物体中识别这些sRNA。
In many bacteria, iron homeostasis is controlled primarily by the ferric uptake regulator (Fur), a transcriptional repressor. However, some genes, including those involved in iron storage, are positively regulated by Fur. A Fur-repressed regulatory small RNA (sRNA), RyhB, has been identified in Escherichia coli, and it has been demonstrated that negative regulation of genes by this sRNA is responsible for the positive regulation of some genes by Fur. No RyhB sequence homologs were found in Pseudomonas aeruginosa, despite the identification of genes positively regulated by its Fur homolog. A bioinformatics approach identified two tandem sRNAs in P. aeruginosa that were candidates for functional homologs of RyhB. These sRNAs (PrrF1 and PrrF2) are >95% identical to each other, and a functional Fur box precedes each. Their expression is induced under iron limitation. Deletion of both sRNAs is required to affect the iron-dependent regulation of an array of genes, including those involved in resistance to oxidative stress, iron storage, and intermediary metabolism. As in E. coli, induction of the PrrF sRNAs leads to the rapid loss of mRNAs for sodB (superoxide dismutase), sdh (succinate dehydrogenase), and a gene encoding a bacterioferritin. Thus, the PrrF sRNAs are the functional homologs of RyhB sRNA. At least one gene, bfrB, is positively regulated by Fur and Fe2+, even in the absence of the PrrF sRNAs. This work suggests that the role of sRNAs in bacterial iron homeostasis may be broad, and approaches similar to those described here may identify these sRNAs in other organisms.